Barrett's Epithelium arises as a complication of chronic reflux esophagitis. In approximately 80% of the cases where chronic reflux esophagitis exists, Barrett's Epithelium arises. In Barrett's Epithelium, the typical stratified squamous epithelium may be replaced by metaplastic columnar epithelial cells. Hence, Barrett's Epithelium predisposes a patient to esophageal carcinoma (Barrett's-derived adenocarcinoma). Barrett's-derived adenocarcinoma develops in approximately 8-15% of all people who have Barrett's Epithelium. See Cameron, et al., "The Incidence of Adenocarcinoma in Columnar-Lined (Barrett's) Esophagus", N. Eng. J. Med., Vol. 313, p. 857-859 (1985).
During the development of Barrett's Epithelium, gastric mucosa extends to the distal esophagus. The morphology of gastric mucosa blends with the transitional zone of Barrett's Epithelium. Because it is difficult to distinguish between gastric mucosa and Barrett's Epithelium, it has been difficult to positively diagnose Barrett's Epithelium. In some cases, cardiac tissue (i.e., tissue from the opening at the upper end of the stomach that connects the stomach and the esophagus) extends to the distal esophagus. This further complicates the diagnosis of Barrett's Epithelium because columnar epithelial cells line the cardiac mucosa. In addition, when cardiac adenocarcinoma extends to the distal esophagus, the histology of the cardiac adenocarcinoma cells resembles Barrett's-derived adenocarcinoma cells, and may be indistinguishable therefrom.
In the past, attempts have been made utilizing enzymatic, histologic and electronmicroscopic features to distinguish Barrett's Epithelium from cardiac cells. However, there has been little success in this area. See Levine, et al., "Specialized Metaplastic Columnar Epithelium in Barrett's Esophagus", Lab Invest., Vol. 60, p. 418-432 (1989). As a result, the diagnosis of benign Barrett's Epithelium and Barrett's-derived adenocarcinoma remain a difficult task, both clinically and pathologically.
It was previously reported that there was a higher frequency of colonic malignancy in patients with Barrett's Esophagus than in a control population. See Sontag, et al., "Barrett's Esophagus and Colonic Tumors", Lancet, Vol. 1, p. 946-948 (1985) and Robertson, et al., "Screening for Colonic Cancer in Patients with Barrett's Esophagus", Brit. Med. J., Vol. 298 (6674), p. 650 (1989). However, it has since been discovered that this is not true. See Abstract No. 44, The American Journal of Gastroenterology, Vol. 86, p. 1301 (1991). In this abstract, Post, et al. conclude that there is no higher prevalence of colonic neoplasis in patients with Barrett's Esophagus than in asymptomatic controls. Therefore, Barrett's Esophagus does not justify colonoscopic surveillance programs. Hence, the prior literature teaches that there is no relationship between colon cancer and esophageal cancer.
Ulcerative Colitis is an autoimmune disease characterized by diarrhea, rectal bleeding, at times fever, loss of weight and chronic ill health. The disease is characterized by acute exacerbation and remission. To date, there is no indication of any relationship between Barrett's Epithelium and Ulcerative Colitis.
The inventor, while studying the pathogenesis of the autoimmune disease Ulcerative Colitis, purified proteins from colon epithelial cell extracts. While studying these colonic epithelial proteins, the inventor developed a monoclonal antibody reactive with such proteins. This monoclonal antibody was designated 7E.sub.12 H.sub.12. The hybridoma secreting the 7E.sub.12 H.sub.12 monoclonal antibody is on deposit with the American Type Culture Collection, Rockville, Md., and is catalogued as ATCC #HB9397. See U.S. patent application Ser. No. 07/841,653 filed Feb. 20, 1992 and Takahashi, F. and Das K. M., "Isolation and Characterization of a Colonic Autoantigen Specifically Recognized by Colon Tissue-Bound Immunoglobulin G From Idiopathic Ulcerative Colitis", J. Clin. Invest., Vol. 76, p. 311-318 (1985).
The inventor has now discovered that the 7E.sub.12 H.sub.12 monoclonal antibody, which is reactive with colonic epithelial proteins, is also reactive with benign Barrett's Epithelium and Barrett's-derived adenocarcinoma, but not with normal esophageal epithelium cells, squamous carcinoma cells, cardia cells, gastric mucosa cells or small intestinal epithelium.
Because the inventor has discovered that colonic epithelium of patients with Ulcerative Colitis, benign Barrett's Epithelium and Barrett's-derived adenocarcinoma cells all share a common epitope, it is now possible to use the 7E.sub.12 H.sub.12 monoclonal antibody and other mononoclonal antibodies which recognize the common epitope to diagnose both benign Barrett's Epithelium and Barrett's-derived adenocarcinoma.
It is therefore an object of this invention to provide a method for diagnosing benign Barrett's Epithelium.
It is another object of this invention to provide a method for diagnosing benign Barrett's Epithelium utilizing monoclonal antibody which reacts with benign Barrett's Epithelium but not with normal esophageal epithelium cells, squamous carcinoma cells, cardia cells or gastric mucosa cells.
It is still another object of this invention to provide a method for diagnosing benign Barrett's Epithelium utilizing monoclonal antibody 7E.sub.12 H.sub.12 which reacts with benign Barrett's Epithelium but not with normal esophageal epithelium cells, squamous carcinoma cells, cardia cells or gastric mucosa cells.
It is a further object of this invention to provide a method for diagnosing Barrett's-derived adenocarcinoma.
It is a still further object of this invention to provide a method for diagnosing Barrett's-derived adenocarcinoma utilizing monoclonal antibody which reacts with Barrett's-derived adenocarcinoma but not with normal esophageal epithelium cells, squamous carcinoma cells, cardia cells or gastric mucosa cells.
It is yet a further object of this invention to provide a method for diagnosing Barrett's-derived adenocarcinoma utilizing monoclonal antibody 7E.sub.12 H.sub.12 which reacts with Barrett's-derived adenocarcinoma but not with normal esophageal epithelium cells, squamous carcinoma cells, cardia cells or gastric mucosa cells.
It is still another object of this invention to provide a method for screening for dysplasia, a condition which indicates a patient's predisposition for Barrett's-derived adenocarcinoma.
It is yet another object of this invention to provide a method for diagnosing benign Barrett's Epithelium and Barrett's-derived adenocarcinoma utilizing an antibody which recognizes an epitope common to colonic epithelium and Barrett's Epithelium.
It is another object of this invention to provide a method for diagnosing benign Barrett's Epithelium and Barrett's-derived adenocarcinoma utilizing an antibody which recognizes an antigen, such antigen also being reactive with monoclonal antibody 7E.sub.12 H.sub.12.